Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17931 (galectin-3)
 2,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The binding of a membrane proteoglycan from a non-encapsulated strain of Klebsiella pneumoniae (Kp-MPG) and four derivatives thereof, to human leukocytes, was investigated by indirect immunofluorescence using biotinylated F(ab')2 fragments of anti-Kp-MPG antibodies and the streptavidin-phycoerythrin amplification system in flow cytometry. Four Kp-MPG derivatives were studied: 1/ an acylpoly(1,3)galactoside (APG), 2/ an APG preparation submitted to acid hydrolysis which removed all fatty acids, but left intact the galactose chain of APG (GC-APG), 3/ a preparation obtained by mild alkaline hydrolysis, containing additional ester-linked C14 and C16 fatty acids bound to the APG molecule (EFA-APG) and 4/ a polymer of the latter compound (APG pol). Kp-MPG, APG and EFA-APG were shown to bind exclusively to monocytes at the lowest concentrations (from 0.15 to 3 microM APG). At higher concentrations, these compounds interacted with polymorphonuclear leukocytes, and with lymphocyte subsets in the following decreasing order: B cells, NK cells, CD8+ and CD4+ lymphocytes. Neither APG pol or GC-APG nor K. pneumoniae smooth LPS showed significant binding to leukocytes. However Kp-LPS treated by drastic alkaline hydrolysis displayed binding properties similar to those of APG. Removal of the ester-linked C14 and C16 fatty acids from EFA-APG did not affect the binding of the molecule. The capacity of cells from the myelomonocytic lineage to bind Kp-MPG and APG was very low in phenotypically immature cell lines (HL60 and U937) as compared with monocytes or polymorphonuclear cells. Treatment of U937 cells with interferon-gamma up-regulated their APG binding capacity along with the expression of the integrin CD 11 b and the CD 14 molecule, whereas monocytes exposed to interferon-gamma showed an increased binding of APG associated with an elevated expression of the galactose specific lectin Mac-2. The data demonstrate a preferential binding of Kp-MPG and APG to cells of the monocyte/macrophage lineage. APG binding does not involve the poly (1,3) galactose chain and the ester-linked C14 and C16 fatty acids but requires the presence of the hydrophobic part of the molecule.
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PMID:Binding of a membrane proteoglycan from Klebsiella pneumoniae and its derivatives to human leukocytes. 149 Jul 26

A cell line, HAFTL-1, derived by in vitro transformation of fetal liver cells with v-Ha-ras, was found to have molecular and phenotypic characteristics of pro-B cells recently committed to the Ly-1+ B cell differentiation pathway. Stimulation of these cells with LPS resulted in their differentiation within either the B or myelomonocytic lineages. Thus, lines derived from LPS-stimulated HAFTL-1 cells were shown to be clonally related, as evidenced by common v-ras integrations, but to exhibit characteristics of pre-B cells (ThB expression, continuing DJ heavy chain rearrangements) or mature macrophages (expression of Mac-1 and Mac-2, lysozyme and nonspecific esterase production, phagocytosis) while maintaining their Ly-1+ phenotype. These results suggest that events resulting in the irrevocable commitment to a single lineage occur late in differentiation, at least within the pathway yielding Ly-1+ B cells and a proposed subpopulation of Ly-1+ monocytes and macrophages. Final commitment to these lineages is carefully orchestrated, as evidenced by restricted expression of Ly-5 isoforms and production of IgH transcripts.
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PMID:Relationships between B cell and myeloid differentiation. Studies with a B lymphocyte progenitor line, HAFTL-1. 329 35

Two monoclonal antibodies, M3/31 and M3/38, were obtained by fusion of mouse myeloma cells with rat spleen cells immunized to immunoadsorbent-purified macrophage glycoproteins. Co-precipitation experiments show that antigenic determinants recognized by these two antibodies reside on the same molecular species, termed Mac-2, Mac-2, an antigen of 32,000 Mr, is synthesized by and expressed on the surface of thioglycollate-elicited macrophages as shown by [35S]-methionine and 125I labeling. Saturation binding experiments show that thioglycollate-elicited macrophages express 1.7 X 10(5) Mac-2 sites/cell. Thioglycollate-elicited macrophages are strongly absorptive for 125I-labeled M3/38 MAb. Kidneys are also absorptive; however, evidence is presented pointing to the nonspecificity of this absorption. Lymph node and thymus are negative, whereas spleen and bone marrow are weakly absorptive, probably due to stromal cells. Nonlymphoid tissues, such as lung, liver, heart, and brain, exhibit slight or no absorbing capacity. Cell suspensions from spleen, bone marrow, thymus, and peripheral lymph node are greater than 99% Mac-2- by immunofluorescent flow cytometry. In contrast, thioglycollate-elicited macrophages are greater than 96% strongly positive for Mac-2. Only 20% of peptone-elicited cells are weakly positive, whereas resident peritoneal macrophages and other macrophage elicited by Listeria monocytogenes, Con A, or LPS are greater than 98% negative. SDS-PAGE of [35S]-methionine-labeled Mac-2 shows that thioglycollate-elicited macrophages synthesize 10- to 30-fold more Mac-2 than other peritoneal macrophage subpopulations, whereas all types of peritoneal macrophages synthesize and express on their surfaces similar amounts of the Mac-1 antigen. Mac-2 antigen is therefore induced in macrophages only in response to specific differentiative signals.
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PMID:Mac-2, a novel 32,000 Mr mouse macrophage subpopulation-specific antigen defined by monoclonal antibodies. 617 26

CD14 is a glycosylphosphatidyl-inositol (GPI)-linked, 55 kDa protein that binds bacterial lipopolysaccharide (LPS, endotoxin) and plays a key role in mediating cellular responses to this potent inflammatory stimulus. Binding of LPS to CD14 is facilitated by serum proteins such as LPS binding protein (LBP). To determine if there are additional plasma proteins that bind to CD14, plasma was passed over immobilized CD14 in the presence or absence of LPS, and retained proteins were eluted. This procedure isolated not only LBP but also a serum protein known as Mac-2-binding protein (Mac-2-BP), a 97 kDa species without a known function. Binding of both LBP and Mac-2-BP to CD14 required the simultaneous presence of LPS. Experiments with purified Mac-2-BP showed that this protein alone neither enabled responses of CD14-bearing cells to LPS nor blocked the ability of plasma to enable responses of CD14-bearing cells to LPS. However, Mac-2-BP did slow the neutralization of LPS mediated by plasma lipoprotein. These studies describe the first potential function for Mac-2-BP, and suggest that neutralization of LPS in plasma may be controlled by proteins in addition to LBP and CD14.
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PMID:LPS-dependent interaction of Mac-2-binding protein with immobilized CD14. 758 57

Galectin-3 is a beta-galactoside binding protein expressed by activated macrophages, epithelial cells, and certain other cell types. Galectin-3 has a C-terminal carbohydrate binding domain, an N-terminal part consisting of a proline- and glycine-rich repetitive domain, and a small N-terminal domain. Two independent LPS binding sites on galectin-3 were demonstrated by binding of biotinylated LPS to immobilized recombinant galectin-3. One appears to be the carbohydrate binding site in the C-terminal domain that confers binding of LPS from Klebsiella pneumoniae that has a beta-galactoside-containing polysaccharide chain. This binding is best demonstrated using galectin-3 immunocaptured by a mAb to the N-terminal part (M3/38) and is inhibited by lactose. In contrast, Salmonella minnesota R7 LPS (Rd mutant), which is devoid of beta-galactosides, appears to bind to a site within the N-terminal part of galectin-3. This interaction is best demonstrated using galectin-3 directly immobilized in wells, and it is inhibited by the Ab M3/38, but not by lactose. Binding inhibition by polymyxin B and the profile of inhibition by a panel of LPSs with different amounts of the inner and outer cores present indicate that this second binding site recognizes the lipid A/inner core region of LPSs.
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PMID:The animal lectin galectin-3 interacts with bacterial lipopolysaccharides via two independent sites. 856 62

Human neutrophils are activated by the beta-galactoside-binding lectin galectin-3, provided that the cells are primed by in vivo extravasation or by in vitro preactivation with, for example, LPS. Removal of terminal sialic acid can change neutrophil functionality and responsiveness due to exposure of underlying glycoconjugate receptors or change in surface charge. Here, we investigated whether such alteration of the cell surface carbohydrate composition can alter the responsiveness of the cells to galectin-3. Neutrophils were treated with neuraminidases (NA) of different origins: Clostridium perfringens (CP), Salmonella typhimurium, Vibrio cholerae, and Newcastle disease virus (NDV). In the presence of NDV-NA, but no other NA, the otherwise non-responding neutrophils responded readily to galectin-3 by activation of the NADPH-oxidase. The galectin-3 priming effect was inhibited by the sialidase inhibitor 2,3-dehydro-2-deoxy-N-acetyl-neuraminic acid. Earlier studies have shown that priming of the neutrophil response to galectin-3 with, for example, LPS is paralleled by degranulation of intracellular vesicles and granules and upregulation of potential galectin-3 receptors. Also, NDV-NA (but not CP-NA) treatment induced degranulation, shown as an upregulation of complement receptor 3. Since not only the galectin response but also the response to the chemoattractant fMLF was primed, NDV-NA appears to induce a general priming phenomenon, possibly due to receptor upregulation by degranulation.
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PMID:Newcastle disease virus neuraminidase primes neutrophils for stimulation by galectin-3 and formyl-Met-Leu-Phe. 1524 63

High blood pressure (HBP) is an important risk factor for cardiac, renal, and vascular dysfunction. Excess inflammation is the major pathogenic mechanism for HBP-induced target organ damage (TOD). N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP), a tetrapeptide specifically degraded by angiotensin converting enzyme (ACE), reduces inflammation, fibrosis, and TOD induced by HBP. Our hypothesis is that Ac-SDKP exerts its anti-inflammatory effects by inhibiting: 1) differentiation of bone marrow stem cells (BMSC) to macrophages, 2) activation and migration of macrophages, and 3) release of the proinflammatory cytokine TNF-alpha by activated macrophages. BMSC were freshly isolated and cultured in macrophage growth medium. Differentiation of murine BMSC to macrophages was analyzed by flow cytometry using F4/80 as a marker of macrophage maturation. Macrophage migration was measured in a modified Boyden chamber. TNF-alpha release by activated macrophages in culture was measured by ELISA. Myocardial macrophage activation in mice with ANG II-induced hypertension was studied by Western blotting of Mac-2 (galectin-3) protein. Interstitial collagen deposition was measured by picrosirius red staining. We found that Ac-SDKP (10 nM) reduced differentiation of cultured BMSC to mature macrophages by 24.5% [F4/80 positivity: 14.09 +/- 1.06 mean fluorescent intensity for vehicle and 10.63 +/- 0.35 for Ac-SDKP; P < 0.05]. Ac-SDKP also decreased galectin-3 and macrophage colony-stimulating factor-dependent macrophage migration. In addition, Ac-SDKP decreased secretion of TNF-alpha by macrophages stimulated with bacterial LPS. In mice with ANG II-induced hypertension, Ac-SDKP reduced expression of galectin-3, a protein produced by infiltrating macrophages in the myocardium, and interstitial collagen deposition. In conclusion, this study demonstrates that part of the anti-inflammatory effect of Ac-SDKP is due to its direct effect on BMSC and macrophage, inhibiting their differentiation, activation, and cytokine release. These effects explain some of the anti-inflammatory and antifibrotic properties of Ac-SDKP in hypertension.
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PMID:Novel anti-inflammatory mechanisms of N-Acetyl-Ser-Asp-Lys-Pro in hypertension-induced target organ damage. 1817 15

Alternative macrophage activation is implicated in diverse disease pathologies such as asthma, organ fibrosis, and granulomatous diseases, but the mechanisms underlying macrophage programming are not fully understood. Galectin-3 is a carbohydrate-binding lectin present on macrophages. We show that disruption of the galectin-3 gene in 129sv mice specifically restrains IL-4/IL-13-induced alternative macrophage activation in bone marrow-derived macrophages in vitro and in resident lung and recruited peritoneal macrophages in vivo without affecting IFN-gamma/LPS-induced classical activation or IL-10-induced deactivation. IL-4-mediated alternative macrophage activation is inhibited by siRNA-targeted deletion of galectin-3 or its membrane receptor CD98 and by inhibition of PI3K. Increased galectin-3 expression and secretion is a feature of alternative macrophage activation. IL-4 stimulates galectin-3 expression and release in parallel with other phenotypic markers of alternative macrophage activation. By contrast, classical macrophage activation with LPS inhibits galectin-3 expression and release. Galectin-3 binds to CD98, and exogenous galectin-3 or cross-linking CD98 with the mAb 4F2 stimulates PI3K activation and alternative activation. IL-4-induced alternative activation is blocked by bis-(3-deoxy-3-(3-methoxybenzamido)-beta-D-galactopyranosyl) sulfane, a specific inhibitor of extracellular galectin-3 carbohydrate binding. These results demonstrate that a galectin-3 feedback loop drives alternative macrophage activation. Pharmacological modulation of galectin-3 function represents a novel therapeutic strategy in pathologies associated with alternatively activated macrophages.
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PMID:Regulation of alternative macrophage activation by galectin-3. 1825 Apr 77

Helicobacter pylori is a prevalent bacterial, gastroduodenal pathogen of humans that can express Lewis (Le) and related antigens in the O-chains of its surface lipopolysaccharide. The O-chains of H. pylori are commonly composed of internal Le(x) units with terminal Le(x) or Le(y) units or, in some strains, with additional units of Le(a), Le(b), Le(c), sialyl-Le(x) and H-1 antigens, as well as blood groups A and B, thereby producing a mosaicism of antigenic units expressed. The genetic determination of the Le antigen biosynthetic pathways in H. pylori has been studied, and despite striking functional similarity, low sequence homology occurs between the bacterial and mammalian alpha(1,3/4)- and alpha(1,2)-fucosyltransferases. Factors affecting Le antigen expression in H. pylori, that can influence the biological impact of this molecular mimicry, include regulation of fucosyltransferase genes through slipped-strand mispairing, the activity and expression levels of the functional enzymes, the preferences of the expressed enzyme for distinctive acceptor molecules and the availability of activated sugar intermediates. Le mimicry was initially implicated in immune evasion and gastric adaptation by the bacterium, but more recent studies show a role in gastric colonization and bacterial adhesion with galectin-3 identified as the gastric receptor for polymeric Le(x) on the bacterium. From the host defence aspect, innate immune recognition of H. pylori by surfactant protein D is influenced by the extent of LPS fucosylation. Furthermore, Le antigen expression affects both the inflammatory response and T-cell polarization that develops after infection. Although controversial, evidence suggests that long-term H. pylori infection can induce autoreactive anti-Le antibodies cross-reacting with the gastric mucosa, in part leading to the development of gastric atrophy. Thus, Le antigen expression and fucosylation in H. pylori have multiple biological effects on pathogenesis and disease outcome.
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PMID:Relevance of fucosylation and Lewis antigen expression in the bacterial gastroduodenal pathogen Helicobacter pylori. 1827 43

Galectin-3 is a beta-galactoside-binding lectin that plays an important role in inflammatory diseases. It also interacts with the surface carbohydrates of many pathogens, including LPS. However, its role in infection is not fully understood. Data presented herein demonstrate for the first time that galectin-3 is a negative regulator of LPS-induced inflammation. Galectin-3 is constitutively produced by macrophages and directly binds to LPS. Galectin-3-deficient macrophages had markedly elevated LPS-induced signaling and inflammatory cytokine production compared with wild-type cells, which was specifically inhibited by the addition of recombinant galectin-3 protein. In contrast, blocking galectin-3 binding sites by using a neutralizing Ab or its ligand, beta-lactose, enhanced LPS-induced inflammatory cytokine expression by wild-type macrophages. In vivo, mice lacking galectin-3 were more susceptible to LPS shock associated with excessive induction of inflammatory cytokines and NO production. However, these changes conferred greater resistance to Salmonella infection. Thus, galectin-3 is a previously unrecognized, naturally occurring, negative regulator of LPS function, which protects the host from endotoxin shock but, conversely, favors Salmonella survival.
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PMID:Galectin-3 is a negative regulator of lipopolysaccharide-mediated inflammation. 1868 69


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